Autoantibodies against M2-muscarinic acetylcholine receptors: new upstream targets in atrial fibrillation in patients with dilated cardiomyopathy

Eur Heart J. 2004 Jul;25(13):1108-15. doi: 10.1016/j.ehj.2004.05.012.

Abstract

Aim: To characterise the clinical significance of M2-muscarinic acetylcholine receptor autoantibodies (M2-AAB) in patients with dilated cardiomyopathy (DCM).

Methods and results: Sera from 104 patients with DCM, age-matched with 104 patients with idiopathic atrial fibrillation (Af) and 104 healthy control subjects, were screened for M2-AAB by enzyme-linked immunosorbent assay (ELISA). IgG purified by Protein-A column was also used as a primary antibody in ELISA. In DCM, M2-AAB were detected in 40% of patients using whole sera and in 36% of patients using purified IgG. M2-AAB were also found in several patients with idiopathic Af (23%, 23%), and these frequencies were significantly higher than those in healthy subjects (8%, 8%). Af was more common in AAB-positive than in AAB-negative patients with DCM. Multivariable analysis confirmed that M2-AAB were independent predictors of the presence of Af in such patients. We determined electrophysiological changes by adding patient purified M2-AAB to chick embryos. Purified IgG from both Af and DCM patients exhibited negative chronotropic effects and induced supraventricular arrhythmias.

Conclusion: M2-AAB may play a role in mediating the development of Af in patients with DCM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atrial Fibrillation / immunology*
  • Autoantibodies / analysis*
  • Cardiomyopathy, Dilated / complications
  • Cardiomyopathy, Dilated / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunoglobulin G / analysis
  • Male
  • Middle Aged
  • Receptor, Muscarinic M2 / immunology*

Substances

  • Autoantibodies
  • Immunoglobulin G
  • Receptor, Muscarinic M2